Pathogenesis Flashcards
Viral pathogenesis:
Viral pathogenesis
the mechanism by which viruses cause disease
series of events that occurs when a virus infects the host
Interplay of viral & host factors, which determines
the nature of infection,
whether disease occurs
the severity of disease
Intro:
Viruses are obligate parasites which must infect cells in order to replicate. This process may result in cell death and dysfunction. The host responds by attempting to rid itself of the virus and the infected cells. Both the viral infection and the host response may contribute to the disease process. The outcome of the infection depends on the balance between viral and host factors.
Viral Infection:
Viral Infection refers to the process by which viruses enter the body, spread to various tissues, localize to target organs, replicate themselves to high levels, and are then shed in order to infect a new host.
Fundamental questions of viral pathogenesis:
How does a virus enter the host?
What is the initial host response?
Where does primary replication occur?
How does the infection spread in the host?
What organs & tissues are infected?
Does it cause disease?
What is the mechanism of disease?
Is the infection cleared from the host or is a persistent infection established?
How is the virus transmitted to other hosts?
How does a virus enter the host?
The natural reservoir is the habitat in which an infectious agent is naturally found and replicates. Reservoirs include humans, animals, and the environment. The reservoir may or may not be the source from which an agent is transferred to a host.
Transmission routes:
- A particular virus will have a specific site which is the preferred entry route, some viruses have >1 entry route
- Viruses are able to enter the body at a particular site, only if the cells have receptors to which the virus can attach
- Viral properties influence the way they are transmitted
- Viruses may or may not cause disease at site of entry, may cause disease at a distant site
Notes on transmission routes:
Viruses need to be able to spread from one host to another in order to survive. Often, organisms use the same portal to enter a new host that they use to exit the source host. Some viruses such as rotavirus, hepatitis A and enteroviruses, secreted in human faeces, are very resistant and can survive for many weeks in the environment. Other viruses such as HIV and many paramyxoviruses are quickly inactivated by drying out and need close contact between humans to be transmitted. The second factor influencing transmission mode is the place where the virus replicates and the amount of virus in a specific compartment: HIV is found in blood and lymphoid tissue and genital secretions, whereas paramyxoviruses are found in respiratory secretions and droplets – thus explaining their different routes of transmission.
The different transmission routes:
Horizontal vs vertical Direct vs indirect Direct contact with infected secretions/lesions Respiratory droplet – coughing, sneezing Airborne Faecal-oral Sexually transmitted Arthropod vector – mosquitoes, ticks Fomites – via inanimate objects Blood borne – needle stick, blood transfusion
Notes:
Notes:
Horizontal transmission - modes of transmission from person to person. Vertical transmission - transfer of infection between parent and offspring (mother to child – transplacental, intrapartum, postnatal, germline). In direct transmission, there is essentially immediate transfer of the agent from a reservoir to a susceptible host by direct contact or droplet spread. Direct contact occurs through kissing, skin-to-skin contact, and sexual intercourse. Droplet spread refers to spray with relatively large, short-range aerosols produced by sneezing, coughing, or even talking. Droplet spread is classified as direct because transmission is by direct spray over a few feet, before the droplets fall to the ground. In indirect transmission, an agent is carried from a reservoir to a susceptible host by suspended air particles or by animate (vector) or inanimate (vehicle) intermediaries. Airborne transmission is by particles that are suspended in air. Droplet nuclei are the residue of dried droplets. The nuclei are less than 5 μ (microns) in size and may remain suspended in the air for long periods, may be blown over great distances, and are easily inhaled into the lungs and exhaled. The route of transmission of many enteric (intestinal) pathogenic agents is described as “faecal oral” because the organisms are shed in faeces, carried on inadequately washed hands, and then transferred through a vehicle (such as food, water, or cooking utensil) to the mouth of a new host. Most vectors are arthropods such as mosquitoes, fleas, and ticks. Viruses that are adapted for a part of their life cycle in a vertebrate host and another part in an arthropod are called arboviruses. These viruses replicate in both the arthropod host (usually in the salivary glands) and the vertebrate host with the arthropods (insects or arachnids such as ticks) transmitting these viruses from the one vertebrate host to the other. Vehicles that may indirectly transmit an agent include food, water, biologic products (blood), and fomites (inanimate objects such as handkerchiefs, bedding, or surgical scalpels).
What is the initial host response? {Where does primary replication occur?
How does the infection spread in the host?
What organs and tissues are infected?}
Local infection:
Localised infection - virus infects the cells at the site of entry & replicates there, spreading to neighbouring cells, but not into the blood, does not spread to the rest of the body
No viraemia occurs, few or no antibodies are detected in the blood
Respiratory & intestinal infections - rapid replication, short incubation period
Local infection examples:
Viral respiratory tract infections eg. rhinovirus, influenza
Viral conjunctivitis eg. adenovirus, enterovirus
Viral gastroenteritis eg. rotavirus, norovirus
Viral skin infection eg. HPV, molluscum contagiosum
Examples of localised infection include rhinovirus infection, which replicates locally in the respiratory tract, but not systemically.
Systemic infection:
The virus usually replicates locally (usually in the mucous membranes) for several days, then drains into the local lymph nodes via the lymphatic system
In the lymph node it replicates again, then released into the blood – primary viraemia
Spreads throughout the body & replicates in permissive organs & tissues - high concentration of virus produced, which then enters the blood - secondary viraemia
Spreads to target organs (eg. the skin in the case of varicella) - in this period the typical clinical picture of the disease usually presents
Secondary viraemia elicits a significant immune response to control the infection
Notes on systemic infection:
The period when the virus is still replicating in the local mucosae is also known as the eclipse period, or the viral eclipse. In the case of mumps and rubella, immune response usually effective; in the case of HIV, the immune system does not eliminate the virus from the body.
Local vs Systemic infection:
The initial entry into the bloodstream is known as the primary viremia. Once in the bloodstream, the virus is then able to reach various organs primarily RES eg liver, lung and kidneys. The virus replicates further in these organs and re-enters the bloodstream at a much higher level. This is known as the secondary viremia. The virus at high levels is then able to infect the target organ. The virus is shed so that it may infect a new host.
Systemic infection:
Faecal oral transmission and respiratory droplet transmission. The initial sites of virus replication include both the pharynx and intestine. Spread to lymph nodes then primary viremia. Replication in organs such as liver/spleen gives rise to secondary viremia with spread to target organs such as CNS for polio.
